Transforming growth factor beta (TGF beta) is a key remodelling factor in asthma. It is produced as a latent complex and the main limiting step in TGF beta bioavailability is its activation. Mast cell tryptase has been shown to stimulate the release of functionally active TGF beta from human airway smooth muscle (ASM) cells [P. Berger, P.O. Girodet, H. Begueret, O. Ousova, D.W. Perng, R. Marthan, A.F. Walls, J.M. Tunon de Lara, Tryptase-stimulated human airway smooth muscle cells induce cytokine synthesis and mast cell chemotaxis, FASEB J. 17 (2003) 2139-2141]. The aim of this study was to determine if tryptase could cause TGF beta activation as well as expression in ASM cells via its receptor, proteinase-activated receptor 2 (PAR2). Tryptase caused TGF beta activation without affecting levels of total TGF beta. This effect was inhibited by the selective tryptase inhibitor FUT175 and leupeptin but not mimicked by the PAR2 activating peptide SLIGKV-NH2. Furthermore, the ASM cells used in the study did not express PAR2. The results indicate that tryptase activates TGF beta via a PAR2-independent proteolytic mechanism in human ASM cells and may help understanding the role of tryptase in asthma. (C) 2008 Elsevier Inc. All rights reserved.